1990 Fiscal Year Final Research Report Summary
Ultraviolet Resonance Raman Spectroscopic Study on the Conformation of Enkephalin and Binding Mode to Receptors
| Project/Area Number |
01470142
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Physical pharmacy
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| Research Institution | Tohoku University |
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Principal Investigator |
TAKEUCHI Hideo Pharmac. Inst. Asoc. Prof., 薬学部, 助教授 (30111454)
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| Co-Investigator(Kenkyū-buntansha) |
HARADA Issei Pharmac. Inst. Prof., 薬学部, 教授 (70011583)
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| Project Period (FY) |
1989 – 1990
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| Keywords | Enkephalin / Opioid / Receptor / UV resonance Raman spectroscopy |
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| Research Abstract |
We have studied the ultraviolet (213- and 240-nm) resonance Raman (UVRR) spectra of Met-enkephalin, Leu-enkephalin, and [Trp^4] Met-enkephalin incorporated into dilauroylphatidylcholine liposomes. The analysis of the spectra based on the data of model compounds obtained previously has provided several pieces of important information on the binding mode of enkephalin to the lipid bilayers. A delta-type opioid receptor has been extracted from rat brain and purified. The structure of the receptor has been investigated by UVRR and circular dichroism spectroscopy. The results obtained are as follows :
1. Every enkephalin mentioned above exists as an ensemble of various extended conformers in aqueous solution, whereas it takes a folded conformation in the lipid-bound state.
2. The Tyr side chain is inserted into the membrane hydrophobic interior, but the Phe side chain is located in the polar surface region or exposed to the aqueous phase.
3. The degree of insertion of Tyr into the membrane is smaller for Leu-enkephalin than the other two.
4. The deeper the Tyr is buried, the higher the affinity and activity of the peptide.
5. The membrane environment is considered to play a role in protecting the N-terminal Tyr form degradation in tissues.
6. The mainchain of the delta-opioid receptor is largely in the beta-sheet structure and the protein does not contain many aromatic residues, particularly Tyr and Typ.
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